An epidemiological study of collagenous colitis in southern Sweden from 2001-2010

AIM: To estimate the incidence of collagenous colitis (CC) in southern Sweden during 2001-2010.METHODS: Cases were identified by searching for CC in the diagnostic registers at the Pathology Departments in the county of Skåne. The catchment area comprised the south-west part of the county (394 307 inhabitants in 2010) and is a mixed urban and rural type with limited migration. CC patients that had undergone colonoscopy during the defined period and were living in this area were included in the study regardless of where in Skåne they had been diagnosed. Medical records were scrutinized and uncertain cases were reassessed to ensure that only newly diagnosed CC cases were included. The diagnosis of CC was based on both clinical and histopathological criteria. The clinical criterion was non-bloody watery diarrhoea. The histopathological criteria were a chronic inflammatory infiltrate in the lamina propria, a thickened subepithelial collagen layer ≥ 10 micrometers (μm) and epithelial damage such as flattening and detachment.RESULTS: During the ten year period from 2001-2010, 198 CC patients in the south-west part of the county of Skåne in southern Sweden were newly diagnosed. Of these, 146 were women and 52 were men, i.e., a female: male ratio of 2.8:1. The median age at diagnosis was 71 years (range 28-95/inter-quartile range 59-81); for women median age was 71 (range 28-95) years and was 73 (range 48-92) years for men. The mean annual incidence was 5.4/10⁵ inhabitants. During the time periods 2001-2005 and 2006-2010, the mean annual incidence rates were 5.4/10⁵ for both periods [95% confidence interval (CI): 4.3-6.5 in 2001-2005 and 4.4-6.4 in 2006-2010, respectively, and 4.7-6.2 for the whole period]. Although the incidence varied over the years (minimum 3.7 to maximum 6.7/10⁵) no increase or decrease in the incidence could be identified. The odds ratio (OR) for CC in women compared to men was estimated to be 2.8 (95% CI: 2.0-3.7). The OR for women 65 years of age or above compared to below 65 years of age was 6.9 (95% CI: 5.0-9.7), and for women 65 years of age or above compared to the whole group the OR was 4.7 (95% CI: 3.6-6.0). The OR for age in general, i.e., above or 65 years of age compared to those younger than 65 was 8.3 (95% CI: 6.2-11.1). During the last decade incidence figures for CC have also been reported from Calgary, Canada during 2002-2004 (4.6/10⁵) and from Terrassa, Spain during 2004-2008 (2.6/10⁵). Our incidence figures from southern Sweden during 2001-2010 (5.4/10⁵) as well as the incidence figures presented in the studies during the 1990s (Terrassa, Spain during 1993-1997 (2.3/10⁵), Olmsted, United States during 1985-2001 (3.1/10⁵), Örebro, Sweden during 1993-1998 (4.9/10⁵), and Iceland during 1995-1999 (5.2/10⁵) are all in line with a north-south gradient, something that has been suggested before both for CC and inflammatory bowel disease.CONCLUSION: The observed incidence of CC is comparable with previous reports from northern Europe and America. The incidence is stable but the female: male ratio seems to be decreasing.     

Hepatitis C virus infection and health-related quality of life

Hepatitis C virus (HCV) hepatitis and other diseases related to HCV, such as cryoglobulinemia, lymphoma and renal failure, impair health-related quality of life (HRQoL). In addition, HCV per se might directly influence HRQoL via colonization of microglia in the brain or, indirectly, via the effect of systemic inflammatory cytokines which, in turn, can trigger brain interleukin production. The treatment of HCV-related disorders with interferon (IFN) has an effect on HRQoL. Initially, IFN causes a transient deterioration of HRQoL, due to the induction of depression and other side effects of treatment. Subsequently, the subjects who obtain a sustained virologic response experience an improvement in HRQoL. Only rarely does interferon treatment causes permanent detrimental effects on HRQoL, due to residual psychiatric or neurologic side effects. Liver transplantation is the only treatment for end-stage HCV-related liver disease. HRQoL generally improves massively a few months after transplantation, except in the case of serious complications of the transplant procedure. Furthermore, high levels of anxiety and neuroticism pre-transplant are associated with lower HRQoL one year after transplant. Additionally, six months after transplant, patients with HCV who experience virologic recurrence show significantly greater depression, anxiety, phobic anxiety, and paranoid ideation than anti-HCV-negative patients. In conclusion, optimal care for the overall well-being of patients with HCV infection requires adequate knowledge of their neurological and psychological status.     

Successful surgical repair of iatrogenic pulmonary vein stenosis

Pulmonary vein stenosis can complicate ablation procedures for atrial fibrillation and often presents with severe respiratory symptoms. Described in this case report is a 21-year-old male who underwent a bilateral surgical augmentation of the pulmonary veins for severe occlusive pulmonary vein stenosis. The occluded left lower and right upper lobe veins were surgically modified to regain flow to the left atrium. Follow-up computed tomogram imaging showed patency of the veins intervened upon and an exercise test demonstrated an oxygen saturation of 98% at peak stress.This case report marks the first-ever surgical intervention for acquired pulmonary vein stenosis.     

Retinoic Acid-related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema

Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.     

Systemic steroids in severe sepsis and septic shock

Despite more than 5 decades of study and debate, the role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial. Data support a beneficial effect on systemic blood pressure in patients with septic shock. However, the ability of corticosteroid therapy to improve mortality in patients with severe sepsis and septic shock remains controversial, with contradictory results from recent large multicenter clinical trials. Although it appears clear that high-dose corticosteroid treatment provides no benefit and possibly harm in septic patients, the experimental design flaws and biases of recent low-dose (physiologic) steroid treatment trials limit their ability to provide adequate answers to the important questions of which septic patients should be treated, how much steroid to give, and the optimum duration of treatment. Unfortunately, the answer to these important questions is not readily evident based on the current evidence or the application of metaanalysis to the available clinical data. This concise evidence-based review highlights the strengths and weaknesses of the current data to inform the practicing clinician as to which patients are likely to derive significant benefit from corticosteroid treatment, while we await more definitive guidance from future multicenter, prospective, randomized, controlled trials designed to better answer these important therapeutic questions.     

Warfarin Therapy in the HIV Medical Home Model: Low Rates of Therapeutic Anticoagulation Despite Adherence and Differences in Dosing Based on Specific Antiretrovirals

Abstract To determine the indications for, rates of therapeutic anticoagulation during, and complications of warfarin therapy in HIV-infected individuals, in whom long-term anticoagulation is frequently indicated. To identify risk factors for nonoptimal anticoagulation and to determine if warfarin dosing is differentially affected by specific antiretroviral agents. Retrospective study of a dedicated anticoagulation program at one of the largest clinics for HIV-infected individuals in the United States. Seventy-three HIV-infected individuals on warfarin were followed for a total of 911 visits. The rate of therapeutic internation normalized ratio (INR) levels was 34.5% when including only visits at which patients were assessed to be adherent with warfarin. In multivariable analysis, injection drug use at baseline was an independent risk factor for subtherapeutic INR (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3-4.7, p=0.01). Additionally, warfarin adherence was protective of both subtherapeutic (OR 0.4, 95% CI 0.2-0.6, p<0.0001) and supratherapeutic (OR 0.5, 95% CI 0.3-0.9, p=0.02) INR status. Efavirenz-based antiretroviral regimens were associated with lower weekly warfarin doses (46?mg) to maintain therapeutic INR compared to lopinavir/ritonavir-based regimens (68?mg; p=0.01) and atazanavir/ritonavir-based regimens (71?mg; p=0.007). Consistently therapeutic warfarin therapy is difficult to achieve in HIV-infected individuals, even with a dedicated anticoagulation program. Adherence to warfarin therapy is important but rates of therapeutic INR levels are nonetheless low. Lower warfarin dosing was required for efavirenz compared to two commonly used protease inhibitor-based regimens. Because of these factors, the emergence of new oral anticoagulants is an important development for HIV-infected individuals who require long term anticoagulation therapy.